Background: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. Methods: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. Results: Twenty-five trials (62.5%, 95% confidence interval = 47.5%–77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%–68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. Conclusion: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.

中文翻译：

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个人随机化的集群：研究设计选择是否适当合理？审查随机试验样本

背景：为了促进试验招募、降低研究成本和提高外部有效性，似乎正在推动更务实的试验，从而出现将集群而不是个体随机化的新原理。这些理由可能是由一种错误的看法驱动的，即选择整群随机化可以减少对知情同意的需求。我们审查了仅涉及个人层面卫生保健干预措施的已发表整群随机试验的随机样本，以确定 (a) 报告选择整群随机化的基本原理的普遍性；(b) 使用整群随机化的明确理由的类型，或者如果没有的话，明显理由；(c) 报告患者知情同意研究干预措施的普遍性；(d) 为放弃同意而提供的理由类型。我们考虑将整群随机试验专门用于评估个人层面的医疗干预措施，重点关注临床试验，在这些试验中，个体随机化仅在理论上是可能的，并且普遍期望获得知情同意。方法：通过在两个电子数据库（Ovid MEDLINE 和 Embase）中实施经过验证的电子搜索过滤器，确定了 40 项整群随机试验的随机样本，两名审查员独立地从每项试验中提取信息。纳入标准如下：2007 年至 2016 年间发表并在加拿大、美国、欧盟、澳大利亚或低中收入国家设置。结果：25 项试验（62.5%，95% 置信区间 = 47.5%–77.5%) 报告了使用集群随机化的明确理由。最常报告的理由是后勤或行政便利（15 项试验，60%）和需要避免污染（13 项试验，52%）；五项试验 (20%) 被引用与推动更实用的试验相关的基本原理。21 项试验（52.5%，95% 置信区间 = 37%–68%）报告了干预的书面知情同意，2 项（5%）报告口头同意，8 项（20%）报告放弃同意，而 9试验 (22.5%) 同意不清楚或未提及。已报告的放弃同意的理由包括临床实践中已经使用了研究干预措施，患者不是单独随机分配的，以及需要促进试验的实用性。只有一项试验根据国际研究伦理指南中的最低标准，即不可行性和最小风险，报告了放弃同意的明确和适当的理由。结论：采用集群而非个体随机化和采用同意豁免的理由正在出现，这与促进实用试验的需要有关。需要更加关注明确报告研究设计原理、知情同意程序以及豁免理由，以确保此类试验符合适当的道德标准。采用集群而不是个体随机化和采用同意豁免的理由正在出现，这与促进实用试验的需要有关。需要更加关注明确报告研究设计原理、知情同意程序以及豁免理由，以确保此类试验符合适当的道德标准。采用集群而不是个体随机化和采用同意豁免的理由正在出现，这与促进实用试验的需要有关。需要更加关注明确报告研究设计原理、知情同意程序以及豁免理由，以确保此类试验符合适当的道德标准。